CTSB p.Ser229=
c.687C>G · rs2230071 · VCV1599666
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.709%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>A here scores Δ0.35 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.27 | GERP -0.66, phastCons 0.96 |
| Overall | ||
| CADD | 1.879 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.709%
African / African-American · 531/74,878 alleles
Filtering AF
0.659%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.64%
Overall
0.0368%
592/1,609,692 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.709% | 141 |
| Admixed American | 0.055% | 1,818 |
| Remaining individualsnot grpmax-eligible | 0.0433% | 2,309 |
| European (non-Finnish) | 8.5e-05% | 1,176,122 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CTSB
- Protein
- p.Ser229=
- Coding
- c.687C>G
- MANE Select
- NM_001908
- dbSNP
- rs2230071
- Type
- single nucleotide variant
- Location
- chr8:11847158 (GRCh38)
- Gene constraint
- LOEUF 1.756 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.95 · 21 PDB
- Residue 229
- a β-strand
Similar variants
- CTSB p.Arg331Pro Uncertain significance ★★ ⚠ same type
- CTSB p.Asp333Asn Uncertain significance ★★ ⚠ same type
- CTSB p.Lys220Glu Uncertain significance ★★ ⚠ same type
- CTSB p.Met73Thr Uncertain significance ★★ ⚠ same type
- CTSB p.Thr332Ala Uncertain significance ★★ ⚠ same type
- CTSB c.327+20C>T Benign ★★ same type
- CTSB c.446+9G>C Benign ★★ same type
- CTSB c.447-16G>C Benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ctsb-p-ser229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown